The long-range objective of this work is an understanding of how bacterial cells regulate their metabolic affairs so as to acheive an orderly yet flexible coordination of the several thousand chemical reactions necessary for growth. The present work in Escherichia coli explores five topics. (a) Catabolic repression. We shall learn how many of the major cellular proteins are sensitive to catabolite charge, what some of these proteins are, and what part the cyclic AMP system plays in this process. (b) Temperature adaptation. We shall examine how much and what kind of temperature-related regulation of the synthesis of individual proteins occurs within the temperature range of unrestricted growth, and we shall test ideas about the factors determining the boundaries of this range. (c) Adaptation to aerobiosis. We shall define the adaptation of E. coli to aerobic and anaerobic growth for the first time in terms of the pattern of regulation of synthesis of individual proteins, finding out how many major proteins are adjusted in response to oxygen, and then learning about their metabolic roles and their regulation. (d) Passive control. We shall evaluate the extent to which passive effects modulate the synthesis of individual proteins, particularly aminoacyl-tRNA synthetases and other parts of the cell's core proteins for making macromolecules. (e) Metabolic regulation. We shall extend our ongoing survey of the regulatory behavior of the major proteins of this organism, and in particular shall refine the definition of the group of proteins that display growth rate-related control, termed metabolic regulation. The study will be conducted with the aid of newly developed techniques for resolving total cell protein and for measuring isotope content of the resolved proteins. Our standardized cell system, including a collection of mutants with conditionally expressed lesions in marcomolecule synthesis, will be used to permit integration of large amounts of quantitative data.